In developed nations, Chlamydia trachomatis is the most common sexually transmitted pathogen. To determine whether prior disease affects the probability of subsequent chlamydial infection, we took culture specimens from 2,546 men and 1,998 women attending a sexually transmitted diseases clinic. The men had nongonococcal urethritis and the women were contacts of men who had a positive chlamydial culture or nongonococcal urethritis. Significantly lower isolation rates for those with a history of sexually transmitted diseases were found for both men (29% vs. 38%; P less than 0.0001) and women (27% vs. 36%; P less than 0.0001). In addition, both men and women with previously documented chlamydial infections had a lower isolation rate at the index visit, if the previous infection occurred less than, as opposed to more than, six months earlier (men: 20% vs. 41%; P = 0.0006; women: 14% vs. 35%; P = 0.003). These relationships were found to be independent of age. However, the effect of partial immunity due to prior infection could not be distinguished from that of prior antibiotic therapy, and if such immunity does confer protection against reinfection, that protection appears to be both partial and of relatively short duration.